Drugs of Abuse: A Pharmacological
Perspective
R. A. (Bob) Lyon, Section Head
R&D Proctor and Gamble
Reviewed by Brian Howells
Outline of drug action in the
central nervous system
The talk began by outlining the
functioning of the central nervous system, wherein the neuron bodies emit
electrical signals along the dendrites to the terminal branches to release
neurotransmitters into the synapse to communicate between nerve cells, etc.,
and the various levels at which drugs can affect this process: before the
synapse (presynaptic) by affecting firing, synthesis storage and release of the
neurotransmitters, or inhibiting their re-uptake so that their effect persists
for longer, or after the synapse (post-synaptic), by interacting with their
receptors to potentiate or block their effects on their target.
They can stimulate, or mimic, the
action of natural substances (agonists, e.g. serotoninergic drugs such as LSD,
which are 5HT-2A agonists) or block this action (antagonists such as Naloxone,
an opioid antagonist).
The language of drugs (Reference USA)
Drugs can be used for medical or
non-medical (“recreational”) purposes. Medical drugs are classified broadly as
over the counter (OTC) or prescription (Rx, ethical); there is also a further
category of “behind the counter” for OTC substances which can be used as
starting materials for illegal drugs (eg. pseudoephededrine, a nasal
decongestant which can be used to make methamphetamine).
Potential drugs of abuse are
“scheduled”, ranging from Schedule 1, with no known medical use and high degree
of danger from abuse (e.g. heroin and LSD), to Schedule 5, with medical use and
low abuse potential (e.g. codeine, an opiate). Benzodiazepine and amphetamines
are 3-4, and cocaine is 2, because of medical use in eye surgery.
Designer drugs are synthetic
drugs employing chemical modification to avoid scheduling. Until identified and
scheduled, they remain legal; however, since they are not subject to any
conventional approval process, they are potentially extremely unsafe.
Route of administration - how the
drug is administered e.g. orally, nasally, by smoking, intravenously, rectally,
vaginally.
Drug delivery device - the device
used to administer the drug, e.g. sugar cube, pipe, syringe, cup.
Addiction: psychological craving
Dependence: a physico-chemical
need for the drug for well-being
Withdrawal: what happens after
cessation in dependents
Tolerance: the need for more in
order to get the same effect
Classes of drugs of
abuse
Central nervous stimulants:
include caffeine, nicotine, amphetamine, cocaine, and “bath salts”. Effects
include high energy/focus and decreased need for sleep.
Caffeine: adenosine
receptor antagonist, side-effects diuresis, nervousness, rapid tolerance,
addictive, leads to dependence (withdrawal effects)
Nicotine: nicotinic
receptor agonist; side effects increased blood pressure and heart rate; rapid
tolerance, addictive, leads to dependence (one of most addictive)
Amphetamines (illegal
synthetics): increase dopamine and norepinephrine release and block reuptake;
side effects increased BP and heart rate, psychosis and long term psychological
changes (schedule 2)
Cocaine: snorted,
smoked or injected in increasing order of effect. Increases dopamine release
and reuptake; side effects increased BP and heart rate (potentially lethal)
(schedule 2 -use as anaesthetic in eye surgery)
“Bath salts”: designer
drugs (mephedrone, methylenedioxypyrovalerone, etc., Ivory Wave, Vanilla Sky,
etc.). Cheap high, effects similar to amphetamine; side effects include
paranoia, hallucinations and suicidal tendencies (schedule 1)
Central nervous system
depressants: include alcohol, opiates/opioids, barbiturates, benzodiazepine;
effects, relaxation, analgesia, sedation
Alcohol (ethanol):
affects acetylcholine, GABA (γ-aminobutyric acid) and NMDA (N-methyl-D-aspartate). Exact mechanism
not fully understood; general depressive effect with dose response from
relaxation to death; side effects foetal alcohol syndrome, alcoholism, liver
disease; tolerance, addictive, leads to dependence. Warning as to the
potentially dangerous effects of combining with a stimulant such as caffeine
and guaraná (e.g. Four Loko)
Opiates/opioids: e.g.
morphine, codeine, thebane; µ opioid receptor agonists; side effects include
constipation; highly addictive/dependency creating (withdrawal)
Barbiturates and
benzodiazepines: GABA receptor agonists; anxiolytics and hypnotics (librium,
valium, rohypnol)
Psychedelics: principal effects
are enhancement or modification of reality
Marijuana: mildly
hallucinogenic, contains delta 9-THC and >60 other cannabinoids which act as
cannabinoid 1 and 2 receptor agonists; effects include euphoria, laughter and relaxation;
side-effects, anxiety, coughing and paranoia
K2; Spice and THC are
more potent and more addictive
LSD, psilocybin,
mescaline, DMT, dimethoxytryptamine (santo daime); serotonin 5HT2A agonists;
effect (8-12 hr) is alteration of experience, vivid colours, the setting
determines the trip; side effects include weakness, jaw clenching and increased
heart rate; rapid dependence, no dependence or addiction; potential
applications to enhance spirituality in terminal patients
Ecstasy, (N-methyl)-3,4-methylenedioxyamphetamine),
MDMA; adrenaline uptake inhibitor, serotonin 5HT2A agonist
Dissociative: e.g. PCP
(phencyclidine), ketamine and dextromethorphan; NMDA antagonists, altering
distribution of glutamate, associated with out of body experience/detachment.
PCP is addictive and
associated with psychotic side effects; ketamine is used as an animal
tranquilizer, and can lead to amnesia, depression and breathing problems at
high doses. Dextromethorphan is an OTC cough suppressant which causes similar
effects at high doses
Saliva divinorum, κ-opioid
agonist, can induce dissociative effects and “visions”; used in Mexican native
religion.
Delirants: alkaloids
atropine and scopolamine are (competitive) muscarinic cholinergic antagonists,
associated with tachycardia and hyperthermia.
Brian
Howells bhsci@uol.com.br
Brian Howells has a bachelor’s degree in agricultural
science and has been a freelance translator from Japanese to English for around
25 years specializing in technical (principally chemical) and patent-related
translation. For the last 20 years he has been living on the beach in São Paulo
state, Brazil.
This comment has been removed by the author.
ReplyDeleteThis a really thorough review of a great session. It was so well structured and full of manageable, practical information. And Brian has taken impressive notes! Dr Lyons was very engaging. He knew the topic inside out and answered our many questions enthusiastically.
ReplyDeleteIt applied so obviously to real life too. I have already raised wine glasses with friends and ended up having a conversation about them being drug delivery devices.
Never discovered such informatory contents
ReplyDeletego